Dr Ray Cook

Next in our series of blogs on Parkinson’s disease, Movement Disorder Neurologist, Dr Paul Silberstein explains the pre-motor phase of Parkinson’s disease. Dr Silberstein discusses how researchers now understand that abnormalities in the nervous system of people living with Parkinson’s disease begin long before physical symptoms are manifest.

The diagnosis of Parkinson’s disease is made on the basis of the motor features of the condition:  slowness of movement, stiffness, tremor, walking and balance impairment.  Whilst these physical symptoms are critical in making a diagnosis, we now understand that abnormalities in the nervous system of people living with Parkinson’s disease begin long before physical symptoms are manifest.

When the brains of people with Parkinson’s disease are examined post mortem under the microscope, typical abnormal inclusions are seen within neurons (brain cells).  These inclusions, known as Lewy bodies, consist of abnormal accumulations of a naturally occurring protein known as alpha synuclein.  These abnormal protein clusters are thought to result in brain cell dysfunction and ultimately in premature brain cell death.

Notably, long before Lewy bodies can be found in the brain of people living with PD, they develop in the nerve cells of the nose and the intestine.  These changes result in loss of sense of smell and constipation, symptoms which are commonly recalled by people living with PD to have been present long before motor symptoms. 

How Lewy bodies, or the processes that result in abnormal protein accumulation  might travel from the nasal and intestinal nerve cells to the brain is not known, but current theories suggest that transport through nerves themselves may be an important mechanism.

Many of the Motor features of Parkinson’s disease (see ‘Motor Features of Parkinson’s Disease‘ blog) relate to a gradual reduction in the ability of the brain to produce a critical brain chemical known as dopamine.  Motor features of PD occur when Lewy bodies are found in the brain’s main dopamine production site – the Substantia Nigra, located at the top of the brain stem.

Prior to involvement of the Substantia Nigra however, pathologic studies have often noted Lewy bodies deposits in even deeper structures in the brain stem.  These structures are involved in regulation of mood and sleep, and likely underscore the common report of patients that they experienced mood or sleep disturbance months or years before they first developed the motor symptoms of PD.

Specific pre-motor features of Parkinson’s disease include Depression and Anxiety.

On the sleep front, common pre-motor symptoms include Restless leg syndrome and REM sleep behaviour disorder, the latter a condition in which patients enact their dreams whilst asleep, leading to movements such punching, kicking or throwing themselves out of bed, all occurring whilst completely asleep.

Pre-motor manifestations of PD including constipation, sleep and mood disturbance commonly respond to symptomatic treatments but are often only linked to the diagnosis of Parkinson’s disease once motor symptoms become manifest.

Understanding the abnormal processes that result in the formation of Lewy bodies and exploration of therapies that might slow or stop this process are a major focus of current research in Parkinson’s disease.